Hiroshima University Research and Technology Guide 2012 Version : Life Science

I Life Science Development of Treatment Strategy for Hepatocellular Carcinoma to Improve the Long Term Prognosis / Hiroshi AIKATA...2 Development of Revolutional Apatite-implant Complex with Simultaneous Bone Augmentation and Osseointegration / Yasumasa AKAGAWA...3 How Do Patients with Alzheimer’s Disease Experience Memory Impairments? / Sawako ARAI...4 Development of New Therapies for Chronic Viral Hepatitis Using Human Hepatocyte Chimeric Mice / Kazuaki CHAYAMA...5 Identification of High Risk Patients to Develop a Pulmonary Arterial Hypertension / Yoshihiro DOHI...6 The Evaluation of the Intractable Chronic Pain in Psychosocial Factor and Specificity Symptom / Mitsuru DOI...7 A Versatile Modification of Physical Properties of Organic Materials by Introduction of Oxaalkyl Chains / Koichi FUKUHARA...8 Activin A Induces Craniofacial Tissue from Undifferentiated Xenopus Ectoderm in vitro / Yasuto FUKUI...9 Functional Analysis of Signal Complexes Containing Insulin Receptor Substrates (IRSs) / Toshiaki FUKUSHIMA...10 Changes in Interhemispheric Inhibition from the Active to Resting Primary Motor Cortex during a Fine-motor Manipulation Task / Kozo FUNASE...11 Creation of High Performance Host Yeast for the Production of Human-type Sphingolipids / Koichi FUNATO...12 Development of New Technologies for the Medicine Using the Chicken Antibodies / Shuichi FURUSAWA...13 Life Science Participation of Plasminogen Activator/Plasmin System in Cell-cell Adhesion and Invasive Growth of Oral Squamous Cell Carcinoma Cells / Tomoaki HAMANA...14 Study on Activation of Salivary Secretory Function with Salivary Gland Massage / Kumiko HARA...15 New Defense System against Invasive Bacteria in Host Cells / Kae HARADA...16 Roles of P/Q Type Voltage-gated Calcium Channel in the Postnatal Development of Neuronal Circuits / Kouichi HASHIMOTO...17 Development of a Variety of Analysis Softwares for Magnetoencephalography / Akira HASHIZUME Part-time Lecturer 18 Genome-wide Profiles of the Core Clock Protein BMAL1 Target by Using Multiple High-throughputApproaches / Fumiyuki HATANAKA...19 Detection Method for Epilepsy Using 11C Flumazenil-PET / Toru HIGAKI...20 Development of the Washing-sterilizer by the Ordinary Pressure Superheated Steam Use / Takamune HINO...21 Functional Diagnosis of Cancers by the Surface Plasmon Resonance Biosensor / Takaaki HIRAGUN...22 Risk Management in Medical Practice / Tooru HIYAMA...23 Generation of Model Mice for Human Diseases and its Application for Development of Novel Therapies / Hiroaki HONDA...24 Cure Rate Improvement of Intractable Hematopoietic Malignancies by Transplantation / Hideo HYODO...25 An Electromagnetophysiological Study on Epileptogenic Zones and Epileptic Spikes UsingIntracranial Electroencephalography andMagnetoencephalography (MEG) in Epilepsy Surgery / Koji IIDA...26 Development of New Antiviral Therapy Using a Chimeric Mouse Human Hepatocytes Infected withHepatitis B Virus (HBV) and Hepatitis C Virus (HCV) / Michio IMAMURA...27 Functional Analysis of RSC Chromatin-Remodeling Complex in Budding Yeast / Yuko IMAMURA...28 Investigation of Interaction of Cancer Stem Cell to Mesenchymal Stem Cell in Oral Cancer / Yasutaka ISHIDA...29 A Study on the Architectural Planning on Children’s Home / Aya ISHIGAKI...30 Health Promotion and Prevention of Sports Injuries / Yoshimasa ISHII...31 Gene Expression Profiles of Idiopathic Interstitial Pneumonias: Identification of Disease-specific Diagnostic Markers and Molecular Therapeutic Targets / Nobuhisa ISHIKAWA...32 New Method for Gastric Cancer Screening by Serum Markers / Masanori ITO...33 Clarification of Signaling Pathway Controlling Breast Cancer / Takayuki KADOYA...34 Remarkable Factors Related to Preventing Relapse of Deciduous Anterior Crossbite / Yasutaka KAIHARA...35 Long-term Tooth Cryopreservation by Use of CAS Freezer / Masato KAKU...36 Characterization of Mesenchymal Stem Cell for Regenerative Therapy / Masami KANAWA...37 Effect of Cholesterol and its Biosynthetic Precursors on the Cause of BRONJ / Taku KANDA...38 Research on Functions of a New Protein Regulating Energy Metabolism / Takashi KANEMATSU...39 Antibody Arrays for Parallel Analysis of Surface Marker Expression / Koichi KATO...40 Novel Functions of Silk Protein, Sericin / Norihisa KATO...41 Regenerative Medicine Using Mesenchymal Stem Cells Expanded with Serum-free Media / Yukio KATO...42 Physical Properties of Food Products and Biomaterials and Their Practical Application / Kiyoshi KAWAI...43 Regulation of Circadian Clock / Takeshi KAWAMOTO...44 Cell Cryopreservation / Toshitsugu KAWATA...45 Stroma-directed Molecular Targeted Therapy in Gastrointestinal Cancer / Yasuhiko KITADAI...46 Development of a Novel Screening and Evaluation System for Useful Peptides by Changing Peptide Utilization Machinery in Yeast / Kenji KITAMURA...47 Identification of Mesenchymal Stem Cell Gene Markers for Quality Control / Kazuko KITAYAMA...(NEDO Grant Contract) 48 Search for Novel Key Role Molecule of Pain Signaling / Tomoya KITAYAMA...49 Construction of the Tongue Pressure and the Lips Pressure Counting System Using a Superthin Pressure Sensor, and its Clinical Application / Myongsun KOH...50 Long-term Effects of Poison Gas Exposure on the Incidence of Respiratory Diseases / Nobuoki KOHNO...51 Utility of KL-6/MUC1 in the Clinical Management of Interstitial Lung Diseases / Nobuoki KOHNO...52 Development of Molecular Target Therapy to VEGF and VEGFR against Oral Cancer / Koichi KOIZUMI...53 Establishment of Standards for Dental Implant Removal with Resorption of Surrounding Bone / Katsunori KORETAKE...54 Molecular Cloning and Analysis of a Biosynthetic Gene Cluster for the Anti-tubercular Agent D-cycloserine / Takanori KUMAGAI...55 Effects of Statin on Serum Fatty Acid Levels / Satoshi KURISU...56 Human Biomechanics Model and Product Usability Evaluation / Yuichi KURITA...57 Tactile and Haptic Models of Humans and Their Applications to Computer Interface / Yuichi KURITA...58 The Morphology and Function of Cells in the Body / Yoshisuke KUSUMOTO...59 Evaluation of the Usefulness of a New Electronic Device for Gingival Massage / Atsue MATSUMOTO...60 Discovery of Bioactive Compounds from Okinawa Subtropical Plants / Katsuyoshi MATSUNAMI...61 Structural and Functional Analysis of Three Enone Reductases from Nicotiana Tabacum / Akihito MATSUSHIMA...62 A Colored Frog Strain for Visual Identification of the Genetic Sex of Tadpole / Ikuo MIURA...63 Functional Analysis of the Gnathodiaphyseal Dysplasia Gene TMEM16E/GDD1 / Kuniko MIZUTA...64 Development of a Novel Kind of Radioprotectors That Inhibit Radiation-induced Cell Death / Akinori MORITA...65 Development of Chronic Disease Management Programs and the Care Delivery System / Michiko MORIYAMA...66 Application of Manufacturing Systems Technology to Dentistry / Takeshi MURAYAMA...67 Development of Protamine as a Protective Agent against Drug-induced Nephrotoxicity / Junya NAGAI...68 Modification of Plant Fundamental Metabolism by the Use of nMat1 Gene / Naoki NAKAGAWA...69 Biomechanical Function of Anterior Cruciate Ligament Remnants / Atsuo NAKAMAE...70 Effects of Knee Immobilization on Regeneration of the Semitendinosus Tendon and on the Proximal Shift of the Semitendinosus Muscle-tendon Junction after Hamstring Harvesting for Anterior Cruciate Ligament Reconstruction: Evaluation Using Three-dimensional Computed Tomography / Atsuo NAKAMAE...71 Development of a New Objective Diagnostic Method for Detecting Motor and Sensory Disturbance Using Higher Brain Function Analysis / Kazuyoshi NAKANISHI...72 Risk Stratification for Brugada Syndrome / Yukiko NAKANO...73 Evaluation of Substance P Content in Biological Samples by Using a High Sensitivity Radioimmunoassay / Yoshihiro NAKATA...74 Simple and Visible Detection Method for Drug and Poison Analysis / Akira NAMERA...75 Yogurt Fermented by Lactobacillus Rhamunosus L8020, Reduce the Risks of Dental Caries, Periodontal Disease and Oral Candidosis / Hiroki NIKAWA...76 Genetic Relationships among Breeds Using Porcine Autosomal SNP Genotypes Using DNA Markers (SNPs) / Masahide NISHIBORI...77 Genetic Variant Associated with the Development of Hepatocellular Carcinoma in Japanese Chronic Hepatitis C Patients / Hidenori OCHI...78 Articular Cartilage Repair with Magnetically Labeled Mesenchymal Stem Cells and External Magnetic Device / Mitsuo OCHI...79 CX3CL1 Expression Induced by Candida Albicans in Oral Fibroblasts / Kouji OHTA...80 Statistical Analysis of Multidimensional Data of Complex Systems / Megu OHTAKI...81 Biodiversity and Ecology of Marine Symbionts and Parasites; Fisheries of Edible Zooplankters / Susumu OHTSUKA...82 Unite for Stroke / Toshiho OHTSUKI...83 Caries Incidence Associated with Streptococcus Mutans and S. Sobrinus in Children / Mitsugi OKADA...84 Upregulation of Notch2 and Six1 is Associated with Progression of Early-stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages / Morihito OKADA...85 Identification of Responsible Genes for Patients with Chronic Mucocutaneous Candidiasis / Satoshi OKADA...86 Research Infrastructure for Conducting a Safe and Secure Cell Therapy Using Mesenchymal Stem Cells Derived from Human Bone Marrow / Kosei OKAMOTO...87 Screening of Useful Materials from Unculturable Bacterial Metagenomes / Yoshiko OKAMURA...88 Assessment of the Safety Behavior in the Workplace / Yasumasa OTSUKA...89 Probabilistic Considerations on Eclosion and Copulation of Cicadas / Yasumasa SAISHO...90 Development of Method to Screen Novel Therapeutical Drugs for Neurodegenerative Disease Using Imaging Technique / Norio SAKAI...91 Evaluation of Dural Arteriovenous Fistulas of Cavernous Sinus before and after Endovascular Treatment Using Time-resolved MR Angiography / Shigeyuki SAKAMOTO...92 Application of Thermally Stable Cytochrome c / Yoshihiro SAMBONGI...93 Prediction of Human Drug Metabolism and Pharmacokinetics Using Chimeric Mice with Humanized Liver / Seigo SANOH...94 Assessment of Trypsinogen-2 levels as an Early Diagnostic for Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis / Tamito SASAKI...95 Functional Model of Temporomandibular Joint / Takahiro SATODA...96 Functional Model of Swallowing / Takahiro SATODA...97 Statistical Data Analysis / Kenichi SATOH...98 Statins Induce Apoptosis and Inhibit Proliferation in Cholangiocarcinoma Cells / Masahiro SERIKAWA...99 A Novel Pig Artificial Insemination Technique Using Frozen-thawed Sperm / Masayuki SHIMADA...100 Intracellular Behavior and Elimination of Extrachromosomal Elements / Noriaki SHIMIZU...101 Mechanism of Gene Amplification and its Application to the Protein Production / Noriaki SHIMIZU...102 Research and Development to Minimize the Impact of Electromagnetic Radiation on the Human Body for Hybrid Vehicles and Electric Vehicles Parts / Kenji SHODAI...(Special Appointment) 103 Development of Simulator for Extracorporeal Circulation / Taijiro SUEDA...104 Spinal Cord Protection during Thoracic Aortic Aneurysm / Taijiro SUEDA...105 Surgery for Atrial Fibrillation / Taijiro SUEDA...106 Neuronal Bases of Pleasure and Displeasure for Taste / Makoto SUGITA...107 See-through Frogs Created by Breeding / Masayuki SUMIDA...108 Clinical Application of an Artificial Nerve for Peripheral Nerve Injury / Osami SUZUKI...109 Treatment of Arthritis Using MicroRNA Th17 Cell Differentiation / Osami SUZUKI...110 Regulation of Gastrointestinal Function by Food Factors / Takuya SUZUKI...111 Medium-chain Acyl-CoA Dehydrogenase (MCAD) Deficiency: Functional Analysis of Mutant Enzymes Found in Japanese Patients / Go TAJIMA...112 Indigenous Symbiotic Environmental Bacteria in the Intestinal Mucosa Drive the Quiescent Mucosal Immune Responses / Ichiro TAKAHASHI...113 Study on Target Gene of miRNA miR224 Which is Overexpressed in Hepatocellular Carcinoma / Shoichi TAKAHASHI...114 Transport of Insulin and its Regulation in Alveolar Epithelial Cells / Mikihisa TAKANO...115 Establishment of Jaw Bone Reconstruction Using High Functional Material for Restoration of the Ideal Jaw Form and the Occlusal Function / Masaaki TAKECHI...116 Survey on Male Dental Hygienists / Toshinobu TAKEMOTO...117 Integrative Analyses of Neuropsychiatric Diseases / Toru TAKUMI...118 Molecular Biology of the Age-related Hearing Loss and Vertigo / Masaya TAKUMIDA...119 Analysis of Chromosome Engineered Mouse Model for Autism / Kota TAMADA...120 Study on Therapeutic Strategy for Colorectal Submucosal Carcinoma after Endoscopic Treatment / Shinji TANAKA...121 Exploitation of MICA Gene Polymorphism for Development of Personalized Medicine in Oral Cancer Patients / Ryouji TANI...122 A New Technology for Treatment of Dental Caries-Regeneration of Tooth Enamel with Amelogenin / Kotaro TANIMOTO...123 Direct Vasodilation by Transdermal Administration of Nitroglycerin: Nitroglycerin Skin Spray for Premedication before Artery Puncture / Keizo TANITAME...124 Development of a Functional Food with an Aim to Enhance Bone Volume / Kazuo TANNE...125 Molecular and Cellular Target Therapy for Hepatic Stellate Cell Using Rho Kinase Inhibitor / Hirotaka TASHIRO...126 Developing the Culture Technology of Pituitary Stem Cell in the Zero Gravity Environment / Atsushi TOMINAGA...127 The Effects on Gene Expression Profiles in Human Hepatocytes by HBV and HCV Infection / Masataka TSUGE...128 Estimation of Arterial Wall Impedance Using Ultra-sonographic Images and its Application to the Diagnosis of Arteriosclerosis / Toshio TSUJI, Masashi KAWAMOTO, Masao YOSHIZUMI...129 Measurement of Peripheral Artery Mechanical Characteristics and Evaluation of Autonomic Nerve Activity / Toshio TSUJI, Masashi KAWAMOTO, Masao YOSHIZUMI...130 Non-constrained and Non-invasive Measurement of Pulse Pressure Waves from Patients in a Supine Position and Development of a Health Monitoring System for Bedridden Individuals / Toshio TSUJI, Masashi KAWAMOTO, Masao YOSHIZUMI...131 Understanding the Mechanism of Chromosome End Maintenance and its Application for Cancer Therapy / Masaru UENO...132 Effect of the Water-soluble Extract from Cultured Medium of Ganoderma Lucidum (Reishi) Mycelia (MAK) on Murine Colitis / Yoshitaka UENO...133 Mechanism, Prediction and Countermeasure of Problematic Jellyfish Blooms / Shin-ichi UYE...134 Mechanism of Chronic Pain in Orofacial Region / Mineo WATANABE...135 Algal Synthesis of Hyaluronan and Chitin / Takashi YAMADA...136 Bacteriophage Biocontrol of Bacterial Wilt for Sustainable Agricultural Production / Takashi YAMADA...137 Detection and Monitoring of Phytopathogen Causing Bacterial Wilt / Takashi YAMADA...138 How Does Habitat Association of Plant Species Generate and Maintain? / Toshihiro YAMADA...139 Neural Regeneration by Application of Human Skull Mesenchymal Stem Cells / Satoshi YAMAGUCHI...140 Development of Engineered Nucleases that Enable the Manipulation of the Genome in Cell Lines and Organisms / Takashi YAMAMOTO...141 Development of Automatic Diagnostic System for Brain Tumors / Fumiyuki YAMASAKI...142 Regulation of Thyroid Hormone Sensitivity by Differential Expression of the Thyroid Hormone Receptor During Xenopus Metamorphosis / Yoshio YAOITA...143 Novel Diagnostic and Therapeutic Targets of Gastrointestinal Cancer Identified by “Omics” Study / Wataru YASUI...144 Clinical and Radiographical Results of 179 Thrust Plate Hip Prosthesis ―5-14 Years Follow-up Study― / Yuji YASUNAGA...145 Biological Psychology of Fish / Masayuki YOSHIDA...146 Quantitative Analysis and Development of a Computer-aided System for Gastrointestinal Lesions Observed on Endoscopy / Shigeto YOSHIDA...147 Assessment of Oral and Pharyngeal Functions for Decision Making of the Ideal Thickness of Liquid / Mineka YOSHIKAWA...148 Purification, Structure Characterization of Bioactive Substances from Marine Organisms and Application to Novel Anti-oral Cancer Drugs / Yukio YOSHIOKA...149 Low Temperature Tolerance of Mammalian Transporters and Development of a New Transport Inhibitor / Ryoko YUMOTO...15

Computational Methods for the Analysis of Genomic Data and Biological Processes

In recent decades, new technologies have made remarkable progress in helping to understand biological systems. Rapid advances in genomic profiling techniques such as microarrays or high-performance sequencing have brought new opportunities and challenges in the fields of computational biology and bioinformatics. Such genetic sequencing techniques allow large amounts of data to be produced, whose analysis and cross-integration could provide a complete view of organisms. As a result, it is necessary to develop new techniques and algorithms that carry out an analysis of these data with reliability and efficiency. This Special Issue collected the latest advances in the field of computational methods for the analysis of gene expression data, and, in particular, the modeling of biological processes. Here we present eleven works selected to be published in this Special Issue due to their interest, quality, and originality

THRB (Thyroid Hormone Receptor, Beta)

Review on THRB, with data on DNA/RNA, on the protein encoded and where the gene is implicated

Pharmacokinetics and Pharmacodynamics of Tyrosine Kinase Inhibitors

__Abstract__ Cancer is the second most common cause of death worldwide after cardiovascular diseases, responsible for an estimated 8.4 million deaths in 2012 and its incidence is still increasing. Through the introduction of many chemotherapeutic agents and hormone treatments in the last decades, treatment options for patients with advanced forms of cancer have improved. Mortality rates have decreased and in some cases cancer is now changing to become a chronic disease. More recent, increased insight in cancer cell biology has led to further improvement in anti-cancer treatment. Much attention has been focused on tyrosine kinases that comprise essential elements of cellular signalling cascades which control proliferation, cell survival and cell death. In cancer, tyrosine kinases can be found activated by mutations, thereby contributing to malignant transformation, tumour growth and metastasis. Targeted therapies, especially tyrosine kinase inhibitors (TKIs), have largely contributed to the recent improvement in anti-cancer treatment. TKIs usually act by competing with adenosine 5’- triphosphate (ATP) for the intracellular ATP binding site of one or more tyrosine kinases. ATP displacement by TKI binding results in inhibition of several processes which are necessary for tumour growth, such as angiogenesis, cell proliferation and cell migration (type I inhibitors). More recently, TKIs have been developed which are non-ATP competitive inhibitors (type II and type III inhibitors). Currently, 17 TKIs are available for the treatment of a broad variety of cancer types, with approval by both the US Food and Drug Administration and European Medicines Agency

Targeted Cancer Therapy and Mechanisms of Resistance

Tumor cells commonly exhibit dependence on a single activated oncogenic pathway or protein to maintain their malignant proliferation and survival, a phenomenon called “oncogene addiction”. According to this concept, protein kinases have been identified as promising molecular targets for cancer therapy. There are several possibilities for targeting these proteins in cancer, including monoclonal antibodies, compounds able to favor the proteolytic degradation of the kinase, small-molecule protein kinase inhibitors (PKIs). Moreover, new anticancer treatments have increasingly been developed focusing on tumor suppressor genes and RNA interference. Despite promising results in cancer treatment with targeted cancer drugs, clinical experience has shown that only a fraction of patients respond to targeted therapies, even if their tumor expresses the altered target. This is known as primary resistance. Otherwise, secondary or acquired resistance to the treatment arises, almost invariably, when tumors are treated with cancer drugs. We set out to select some studies containing emerging developments on the subject. In essence, this collection aims to highlight some recent findings regarding resistance mechanisms and reviews of molecular targeting and resistance with 14 contributions, including 10 original research papers and 4 reviews. Aspects relating to solid cancers, such as breast, ovary, colon, and blood cancers such as leukemia, and the identification of resistance mechanisms and new molecular targets, help to create the basis for the preclinical and clinical development of more effective next-generation drugs

GENETIC ANALYSIS OF THE HIPPO PATHWAY IN MOUSE LIVER

Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing exons in each component (Mst1, Mst2, Sav1, Lats1 and Lats2). These mice were then crossed with different cre-mouse lines to generate conditional knockout mice. Results indicate a ubiquitous tumor suppression function of these components, predominantly in the liver. A further liver specific analysis of the deletion mutation of these components, as well as the Yap/Taz double deletion mutation, reveals essential roles of the Hippo pathway in regulating hepatic quiescence and embryonic liver development. One of the key cellular mechanisms for the Hippo pathway’s involvement in these liver biological events is likely its cell cycle regulation function. Our work will help to develop potential therapeutic approaches for liver cancer

Future Aspects of Tumor Suppressor Gene

Tumor suppressor genes (TSGs) and their signaling networks are fast growing areas in current biomedical science. These groups of genes, which are not limited to tumor suppression, play critical roles in many cellular activities. This book, "Future Aspects of Tumor Suppressor Genes", contains some fascinating fields, from basic to translational researches, in recent TSG studies. For example, several TSG signaling pathways are addressed in this book, and both mouse and Drosophila models used for the exploration of these genes are described based on the experimental evidence. A detailed review for current knowledge of microRNA studies in the regulation of tumor growth is introduced. Additionally, how natural compounds interfere with the progression of cancer development via TSG pathways is systemically summarized. Recent progresses in cell reprogramming and stemness transition processes regulated by TSG pathways are also included in this book